Tumor-related HSP70 released after cryo-thermal therapy targeted innate immune initiation in the antitumor immune response
Purpose In our previous study, a novel cryo-thermal therapy that could stimulate the maturation of innate immune cells to subsequently activate the CD4+Th1 cell-dominated antitumor response was developed. However, why cryo-thermal therapy can induce the maturation of innate immunity remains unknown....
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2020-01-01
|
| Series: | International Journal of Hyperthermia |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/02656736.2020.1788173 |
| _version_ | 1818607200983056384 |
|---|---|
| author | Jun Zhu Yue Lou Ping Liu Lisa X. Xu |
| author_facet | Jun Zhu Yue Lou Ping Liu Lisa X. Xu |
| author_sort | Jun Zhu |
| collection | DOAJ |
| description | Purpose In our previous study, a novel cryo-thermal therapy that could stimulate the maturation of innate immune cells to subsequently activate the CD4+Th1 cell-dominated antitumor response was developed. However, why cryo-thermal therapy can induce the maturation of innate immunity remains unknown. Methods In this study, western blot and ELISA were used to analyze the levels of damage-associated molecular patterns (DAMPs, including heat shock protein 70 (HSP70), calreticulin and high-mobility group box protein 1) in situ and in the peripheral blood at different times after cryo-thermal therapy or traditional radiofrequency ablation. The effects of these three DAMPs on myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs) and macrophages were investigated by antibody neutralization in vitro. The phenotypic and functional changes in MDSCs, DCs and macrophages were analyzed using FACS and qRT-PCR. An anti-HSP70 antibody was injected intravenously at 6 h after cryo-thermal therapy on days 1 and 2 and mouse survival was monitored. Results Cryo-thermal therapy could trigger the release of DAMPs in situ and in the peripheral circulation, which could downregulate the proportion and suppressive signature of MDSCs, and promote the M1 macrophages polarization and DCs maturation. Among three DAMPs, HSP70 played the most evident role in M1 macrophage polarization. In vivo neutralization of HSP70 in the early stage of treatment could significantly decrease the survival rate of cryo-thermal therapy treated mice. Conclusions Local cryo-thermal therapy not only destroyed solid tumors thermally and mechanically but also induced the release of a large amount of DAMPs to effectively trigger a systemic antitumor response. |
| first_indexed | 2024-12-16T14:22:59Z |
| format | Article |
| id | doaj.art-f88e5429623941c1ba01315c2ca12a83 |
| institution | Directory Open Access Journal |
| issn | 0265-6736 1464-5157 |
| language | English |
| last_indexed | 2024-12-16T14:22:59Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | International Journal of Hyperthermia |
| spelling | doaj.art-f88e5429623941c1ba01315c2ca12a832022-12-21T22:28:27ZengTaylor & Francis GroupInternational Journal of Hyperthermia0265-67361464-51572020-01-0137184385310.1080/02656736.2020.17881731788173Tumor-related HSP70 released after cryo-thermal therapy targeted innate immune initiation in the antitumor immune responseJun Zhu0Yue Lou1Ping Liu2Lisa X. Xu3School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversityPurpose In our previous study, a novel cryo-thermal therapy that could stimulate the maturation of innate immune cells to subsequently activate the CD4+Th1 cell-dominated antitumor response was developed. However, why cryo-thermal therapy can induce the maturation of innate immunity remains unknown. Methods In this study, western blot and ELISA were used to analyze the levels of damage-associated molecular patterns (DAMPs, including heat shock protein 70 (HSP70), calreticulin and high-mobility group box protein 1) in situ and in the peripheral blood at different times after cryo-thermal therapy or traditional radiofrequency ablation. The effects of these three DAMPs on myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs) and macrophages were investigated by antibody neutralization in vitro. The phenotypic and functional changes in MDSCs, DCs and macrophages were analyzed using FACS and qRT-PCR. An anti-HSP70 antibody was injected intravenously at 6 h after cryo-thermal therapy on days 1 and 2 and mouse survival was monitored. Results Cryo-thermal therapy could trigger the release of DAMPs in situ and in the peripheral circulation, which could downregulate the proportion and suppressive signature of MDSCs, and promote the M1 macrophages polarization and DCs maturation. Among three DAMPs, HSP70 played the most evident role in M1 macrophage polarization. In vivo neutralization of HSP70 in the early stage of treatment could significantly decrease the survival rate of cryo-thermal therapy treated mice. Conclusions Local cryo-thermal therapy not only destroyed solid tumors thermally and mechanically but also induced the release of a large amount of DAMPs to effectively trigger a systemic antitumor response.http://dx.doi.org/10.1080/02656736.2020.1788173cryo-thermal therapydampsmdscsm1 macrophages polarizationdcs maturation |
| spellingShingle | Jun Zhu Yue Lou Ping Liu Lisa X. Xu Tumor-related HSP70 released after cryo-thermal therapy targeted innate immune initiation in the antitumor immune response International Journal of Hyperthermia cryo-thermal therapy damps mdscs m1 macrophages polarization dcs maturation |
| title | Tumor-related HSP70 released after cryo-thermal therapy targeted innate immune initiation in the antitumor immune response |
| title_full | Tumor-related HSP70 released after cryo-thermal therapy targeted innate immune initiation in the antitumor immune response |
| title_fullStr | Tumor-related HSP70 released after cryo-thermal therapy targeted innate immune initiation in the antitumor immune response |
| title_full_unstemmed | Tumor-related HSP70 released after cryo-thermal therapy targeted innate immune initiation in the antitumor immune response |
| title_short | Tumor-related HSP70 released after cryo-thermal therapy targeted innate immune initiation in the antitumor immune response |
| title_sort | tumor related hsp70 released after cryo thermal therapy targeted innate immune initiation in the antitumor immune response |
| topic | cryo-thermal therapy damps mdscs m1 macrophages polarization dcs maturation |
| url | http://dx.doi.org/10.1080/02656736.2020.1788173 |
| work_keys_str_mv | AT junzhu tumorrelatedhsp70releasedaftercryothermaltherapytargetedinnateimmuneinitiationintheantitumorimmuneresponse AT yuelou tumorrelatedhsp70releasedaftercryothermaltherapytargetedinnateimmuneinitiationintheantitumorimmuneresponse AT pingliu tumorrelatedhsp70releasedaftercryothermaltherapytargetedinnateimmuneinitiationintheantitumorimmuneresponse AT lisaxxu tumorrelatedhsp70releasedaftercryothermaltherapytargetedinnateimmuneinitiationintheantitumorimmuneresponse |